It has been suggested that p16 has a role in glucocorticoid (GC)-related apoptosis in leukemic cells, but the exact mechanisms have yet to be clarified. We evaluated the relationship between the GC response and p16 expression in a lymphoma cell line.

We used p16 siRNA transfection to construct p16-inactivated cells by using the B-cell lymphoblast cell line NC-37. We compared glucocorticoid receptor (GR) expression, apoptosis, and cell viability between control (p16+ NC-37) and p16 siRNA-transfected (p16- NC-37) cells after a single dose of dexamethasone (DX).

In both groups, there was a significant increase in cytoplasmic GR expression, which tended to be higher for p16+ NC-37 cells than for p16- NC37 cells at all times, and the difference at 18 h was significant ( P <0.05). Similar patterns of early apoptosis were observed in both groups, and late apoptosis occurred at higher levels at 18 h when the GR had already been downregulated ( P <0.05). Cell viability decreased in both groups but the degree of reduction was more severe in p16+ NC-37 cells after 18 h ( P <0.05).

These results suggest a relationship between GR expression and cell cycle inhibition, in which the absence of p16 leads to reduced cell sensitivity to DX.